Tumor microenvironment is essential for multiple myeloma (MM) growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM) microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management. 1. Tumor-Associated Macrophages In the past decades, the major focus of cancer research has been the malignant cell itself. In haematological malignancies, including multiple myeloma (MM), this has led to the identification of molecular alterations affecting growth control and apoptotic pathways [1]. Recent studies add yet another facet to the complex multistep model of tumorigenesis by demonstrating that tumor cells carrying genomic and epigenomic abnormalities also trigger changes in their microenvironment [2]. Indeed, accumulating evidence supports the hypothesis that the tumor microenvironment or “niche” ultimately determines the clinical behavior of the disease and has direct impact on overall prognosis [3]. MM is characterized by the accumulation of monoclonal plasma cells in the bone marrow (BM) where they grow and expand. This suggests the importance of the BM microenvironment in supporting MM cell growth and survival [4]. The roles of BM stromal cells in supporting MM plasma cells have been extensively studied. The interaction between plasma cells and stromal cells confers plasma cell homing, growth, survival, and resistance to chemotherapy [5]. Among stromal cells, the inflammatory cells play an indispensable role in disease progression [6]. Within the tumor stroma, the macrophage is the pivotal member of inflammatory cells. Tumor-associated macrophages (TAMs), which constitute a significant part of
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